Dementia diagnosis and referral in general practice: a representative survey of Irish general practitioners

Aims: Most of those with a memory problem or concern over cognition present to their General Practitioner (GP) in the first instance. Despite this, the current diagnostic and referral patterns of Irish GPs remains unclear. Methods: A survey was distributed to three separate cohorts of GPs (n=692) Results: Ninety-Five (14%) responded. Most personally diagnose 1-3 (69%; 65/95) or 4-6 (21%; 20/95) patients with dementia per year. Two-thirds (62%; 59/95) refer >80% of those with possible dementia for further assessment/support, most commonly to support/clarify a diagnosis (71%; 67/95) and most frequently to a geriatrician (79%; 75/95). In half of cases (51%; 48/95), referral is to a professional working as part of an established memory clinic. One-fifth reported receiving dementia-specific postgraduate training (19%; 18/95) and over four-fifths (82%; 78/95) would welcome further training. Discussion: Further attention to the ongoing establishment of memory clinic services and dedicated referral pathways, as well as increasing emphasis on dementia assessment and diagnosis in medical curricula, is warranted

Gait Characteristics and Cognitive Function in Middle-Aged Adults With and Without Type 2 Diabetes Mellitus: Data from ENBIND

Type 2 Diabetes Mellitus (T2DM) in midlife is associated with a greater risk of dementia in later life. Both gait speed and spatiotemporal gait characteristics have been associated with later cognitive decline in community-dwelling older adults. Thus, the assessment of gait characteristics in uncomplicated midlife T2DM may be important in selecting-out those with T2DM at greatest risk of later cognitive decline. We assessed the relationship between Inertial Motion Unit (IMUs)- derived gait characteristics and cognitive function assessed via Montreal Cognitive Assessment (MOCA)/detailed neuropsychological assessment battery (CANTAB) in middle-aged adults with and without uncomplicated T2DM using both multivariate linear regression and a neural network approach. Gait was assessed under (i) normal walking, (ii) fast (maximal) walking and (iii) cognitive dual-task walking (reciting alternate letters of the alphabet) conditions. Overall, 138 individuals were recruited (n = 94 with T2DM; 53% female, 52.8 8.3 years; n = 44 healthy controls, 43% female, 51.9 8.1 years). Midlife T2DM was associated with significantly slower gait velocity on both slow and fast walks (both p \u3c 0.01) in addition to a longer stride time and greater gait complexity during normal walk (both p \u3c 0.05). Findings persisted following covariate adjustment. In analyzing cognitive performance, the strongest association was observed between gait velocity and global cognitive function (MOCA). Significant associations were also observed between immediate/delayed memory performance and gait velocity. Analysis using a neural network approach did not outperform multivariate linear regression in predicting cognitive function (MOCA) from gait velocity. Our study demonstrates the impact of uncomplicated T2DM on gait speed and gait characteristics in midlife, in addition to the striking relationship between gait characteristics and global cognitive function/memory performance in midlife. Further studies are needed to evaluate the longitudinal relationship between midlife gait characteristics and later cognitive decline, which may aid in selecting-out those with T2DM at greatest-risk for preventative interventions

Cold-atom shaping with MEMS scanning mirrors

We demonstrate the integration of micro-electro-mechanical-systems (MEMS) scanning mirrors as active elements for the local optical pumping of ultra-cold atoms in a magneto-optical trap. A pair of MEMS mirrors steer a focused resonant beam through a cloud of trapped atoms shelved in the \textit{F}=1 ground-state of \textsuperscript{87}Rb for spatially-selective fluorescence of the atom cloud. Two-dimensional control is demonstrated by forming geometrical patterns along the imaging axis of the cold atom ensemble. Such control of the atomic ensemble with a microfabricated mirror pair could find applications in single atom selection, local optical pumping and arbitrary cloud shaping. This approach has significant potential for miniaturisation and in creating portable control systems for quantum optic experiments.Comment: 4 pages, 3 figure

Enabling the mass production of a chip-scale laser cooling platform

A low-cost, mass-producible laser-cooling platform would have a transformative effect in the burgeoning field of quantum technologies and the wider research of atomic sensors. Recent advancements in the micro-fabrication of diffractive optics and vacuum apparatus have paved the way for a simple, stackable solution to the laser cooling of alkali atoms. In this paper we will highlight our recent investigations into a chip-scale, cold-atom platform, outlining our approach for on-chip wavelength referencing, examining a solution for imaging atoms in a planar stacked device, and finally discussing the limitations to passively pumped vacuum longevity. These results will be discussed in the context of an outlined road-map for the production and commercialisation of chip-scale, cold-atom sensors

Antidepressant use and orthostatic hypotension in older adults living with mild-to-moderate Alzheimer disease

Objectives: Antidepressant use is often reported as a risk factor for Orthostatic Hypotension (OH), however this relationship has never been explored in those with mild/moderate Alzheimer Disease (AD), who may represent a particularly vulnerable cohort. Methods: We performed a cross‐sectional analysis of baseline data from the NILVAD study. Participants with mild‐moderate AD were recruited from 23 centres in nine countries. Systolic and Diastolic Blood Pressure (SBP/DBP) was recorded in the seated position and after both 1 and 5 minutes of standing. OH was defined as a drop of ≥20 mmHg SBP/≥10 mmHg DBP. We examined the relationship between antidepressant use, orthostatic BP drop and the presence of OH, controlling for important covariates. Results: Of 509 participants (72.9 ± 8.3 years, 61.9% female), two‐fifths (39.1%; 199/509) were prescribed a regular antidepressant. Antidepressant use was associated with a significantly greater SBP and DBP drop at 5 minutes (β: 1.83, 0.16‐3.50, P = .03 for SBP; β: 1.13, 0.02‐2.25, P < .05 for DBP). Selective Serotonin Reuptake Inhibitor (SSRI) use was associated with a significantly greater likelihood of OH (OR 2.0, 1.1‐3.6, P = .02). Both findings persisted following robust covariate adjustment. Conclusions: In older adults with AD, antidepressants were associated with a significantly greater SBP/DBP drop at 5 minutes. SSRI use in particular may be a risk factor for OH. This emphasises the need to screen older antidepressant users, and particularly those with AD, for ongoing orthostatic symptoms in order to reduce the risk of falls in this vulnerable cohort

Floral temperature and optimal foraging: is heat a feasible floral reward for pollinators?

As well as nutritional rewards, some plants also reward ectothermic pollinators with warmth. Bumble bees have some control over their temperature, but have been shown to forage at warmer flowers when given a choice, suggesting that there is some advantage to them of foraging at warm flowers (such as reducing the energy required to raise their body to flight temperature before leaving the flower). We describe a model that considers how a heat reward affects the foraging behaviour in a thermogenic central-place forager (such as a bumble bee). We show that although the pollinator should spend a longer time on individual flowers if they are warm, the increase in total visit time is likely to be small. The pollinator's net rate of energy gain will be increased by landing on warmer flowers. Therefore, if a plant provides a heat reward, it could reduce the amount of nectar it produces, whilst still providing its pollinator with the same net rate of gain. We suggest how heat rewards may link with plant life history strategies

Characterisation of the pro-inflammatory cytokine signature in severe COVID-19

Clinical outcomes from infection with SARS-CoV-2, the cause of the COVID-19 pandemic, are remarkably variable ranging from asymptomatic infection to severe pneumonia and death. One of the key drivers of this variability is differing trajectories in the immune response to SARS-CoV-2 infection. Many studies have noted markedly elevated cytokine levels in severe COVID-19, although results vary by cohort, cytokine studied and sensitivity of assay used. We assessed the immune response in acute COVID-19 by measuring 20 inflammatory markers in 118 unvaccinated patients with acute COVID-19 (median age: 70, IQR: 58-79 years; 48.3% female) recruited during the first year of the pandemic and 44 SARS-CoV-2 naïve healthy controls. Acute COVID-19 was associated with marked elevations in nearly all pro-inflammatory markers, whilst eleven markers (namely IL-1β, IL-2, IL-6, IL-10, IL-18, IL-23, IL-33, TNF-α, IP-10, G-CSF and YKL-40) were associated with disease severity. We observed significant correlations between nearly all markers elevated in those infected with SARS-CoV-2 consistent with widespread immune dysregulation. Principal component analysis highlighted a pro-inflammatory cytokine signature (with strongest contributions from IL-1β, IL-2, IL-6, IL-10, IL-33, G-CSF, TNF-α and IP-10) which was independently associated with severe COVID-19 (aOR: 1.40, 1.11-1.76, p=0.005), invasive mechanical ventilation (aOR: 1.61, 1.19-2.20, p=0.001) and mortality (aOR 1.57, 1.06-2.32, p = 0.02). Our findings demonstrate elevated cytokines and widespread immune dysregulation in severe COVID-19, adding further evidence for the role of a pro-inflammatory cytokine signature in severe and critical COVID-19

Air-sea CO2 exchange in the equatorial Pacific

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 109 (2004): C08S02, doi:10.1029/2003JC002256.GasEx-2001, a 15-day air-sea carbon dioxide (CO2) exchange study conducted in the equatorial Pacific, used a combination of ships, buoys, and drifters equipped with ocean and atmospheric sensors to assess variability and surface mechanisms controlling air-sea CO2 fluxes. Direct covariance and profile method air-sea CO2 fluxes were measured together with the surface ocean and marine boundary layer processes. The study took place in February 2001 near 125°W, 3°S in a region of high CO2. The diurnal variation in the air-sea CO2 difference was 2.5%, driven predominantly by temperature effects on surface solubility. The wind speed was 6.0 ± 1.3 m s−1, and the atmospheric boundary layer was unstable with conditions over the range −1 < z/L < 0. Diurnal heat fluxes generated daytime surface ocean stratification and subsequent large nighttime buoyancy fluxes. The average CO2 flux from the ocean to the atmosphere was determined to be 3.9 mol m−2 yr−1, with nighttime CO2 fluxes increasing by 40% over daytime values because of a strong nighttime increase in (vertical) convective velocities. The 15 days of air-sea flux measurements taken during GasEx-2001 demonstrate some of the systematic environmental trends of the eastern equatorial Pacific Ocean. The fact that other physical processes, in addition to wind, were observed to control the rate of CO2 transfer from the ocean to the atmosphere indicates that these processes need to be taken into account in local and global biogeochemical models. These local processes can vary on regional and global scales. The GasEx-2001 results show a weak wind dependence but a strong variability in processes governed by the diurnal heating cycle. This implies that any changes in the incident radiation, including atmospheric cloud dynamics, phytoplankton biomass, and surface ocean stratification may have significant feedbacks on the amount and variability of air-sea gas exchange. This is in sharp contrast with previous field studies of air-sea gas exchange, which showed that wind was the dominating forcing function. The results suggest that gas transfer parameterizations that rely solely on wind will be insufficient for regions with low to intermediate winds and strong insolation.This work was performed with the support of the National Science Foundation Grant OCE-9986724 and the NOAA Global Carbon Cycle Program Grants NA06GP048, NA17RJ1223, and NA87RJ0445 in the Office of Global Programs

Potentially inappropriate medication use in older adults with mild-moderate Alzheimer's disease:Prevalence and associations with adverse events

Aim: Potentially inappropriate medication (PIM) use is prevalent in older adults and is associated with adverse events, hospitalisation and mortality. We assessed the patterns and associations of PIM use in older adults with mild-to-moderate Alzheimer's Disease (AD), who may represent a particularly vulnerable group. Design: Analysis of data from NILVad, an 18-month Randomised Control Trial of Nilvadapine in mild-to-moderate AD. The v2 STOPP criteria were applied in duplicate to identify PIM use. Associations between PIM use and adverse events/unscheduled healthcare visits in addition to the associations between PIM use and AD progression were evaluated. Setting and Participants: 448 older adults with mild-to-moderate AD from 23 centres in nine European countries. Results: Of 448 participants (mean age: 72.56 ± 8.19 years), over half (55.8%) were prescribed a PIM with 30.1% being prescribed 2+ PIMs. The most frequent PIMs were (i) long-term benzodiazepines (11.6% N = 52/448), (ii) selective serotonin reuptake inhibitors without appropriate indication (11.1% N = 50/448), and (iii) Proton-Pump Inhibitors (PPIs) without appropriate indication (10.7% N = 48/448). Increasing number of PIMs was associated with a greater risk of adverse events (IRR 1.17, 1.13-1.19, P &lt; 0.001), serious adverse events (IRR 1.27; 1.17-1.37, P &lt; 0.001), unscheduled hospitalisations (IRR 1.16, 1.03-1.30, P = 0.016) and GP visits (IRR 1.22, 1.15-1.28, P &lt; 0.001). PIM use was not associated with dementia progression. Conclusions and Implications: PIM use is highly prevalent in mild-to-moderate AD and is associated with adverse events and unscheduled healthcare utilisation. Further attention to de-prescribing in this vulnerable group is warranted

Understanding the influences on successful quality improvement in emergency general surgery: learning from the RCS Chole-QuIC project

Abstract: Background: Acute gallstone disease is the highest volume Emergency General Surgical presentation in the UK. Recent data indicate wide variations in the quality of care provided across the country, with national guidance for care delivery not implemented in most UK hospitals. Against this backdrop, the Royal College of Surgeons of England set up a 13-hospital quality improvement collaborative (Chole-QuIC) to support clinical teams to reduce time to surgery for patients with acute gallstone disease requiring emergency cholecystectomy. Methods: Prospective, mixed-methods process evaluation to answer the following: (1) how was the collaborative delivered by the faculty and received, understood and enacted by the participants; (2) what influenced teams’ ability to improve care for patients requiring emergency cholecystectomy? We collected and analysed a range of data including field notes, ethnographic observations of meetings, and project documentation. Analysis was based on the framework approach, informed by Normalisation Process Theory, and involved the creation of comparative case studies based on hospital performance during the project. Results: Chole-QuIC was delivered as planned and was well received and understood by participants. Four hospitals were identified as highly successful, based upon a substantial increase in the number of patients having surgery in line with national guidance. Conversely, four hospitals were identified as challenged, achieving no significant improvement. The comparative analysis indicate that six inter-related influences appeared most associated with improvement: (1) achieving clarity of purpose amongst site leads and key stakeholders; (2) capacity to lead and effective project support; (3) ideas to action; (4) learning from own and others’ experience; (5) creating additional capacity to do emergency cholecystectomies; and (6) coordinating/managing the patient pathway. Conclusion: Collaborative-based quality improvement is a viable strategy for emergency surgery but success requires the deployment of effective clinical strategies in conjunction with improvement strategies. In particular, achieving clarity of purpose about proposed changes amongst key stakeholders was a vital precursor to improvement, enabling the creation of additional surgical capacity and new pathways to be implemented effectively. Protected time, testing ideas, and the ability to learn quickly from data and experience were associated with greater impact within this cohort